Background Activation of components of the phosphatidylinositol 3 kinase (PI3K) pathway is a recurrent event in breast cancer through inactivation of PTEN function and overexpression of multiple upstream (HER2 family members) and downstream components of the pathway (AKT2, p70S6K). Studies from our laboratory and others in this PPG have implicated these events in the initiation, progression and outcome of breast cancer in both humans and animal models. Preliminary Data Our preliminary data suggests that the p85 regulatory component of the p85/p110 PI3K heterodimer plays a critical role as a linker molecule recruiting a number of important cellular mediators to the activation nidus and placing them in the context of activated p110 as well as tyrosine kinases and other regulatory molecules. Preventing this recruitment results in a G2M arrest followed by cell death. Rationale An exploration of the linker function and regulation of p85 will contribute to an improved understanding of the initiation and progression of breast cancer and identify novel targets for therapy. Hypothesis: That the p85 subunit of PI3K plays a critical role in the regulation of breast cancer initiation and progression through its ability to recruit Racl, PAK1 and other interacting molecules in addition to the p110 catalytic subunit of PI3K to the activation nidus created by stimulation of cell surface receptors. Specific Aims To accomplish this, we will perform three aims. Specific Aim 1 What is the role of p85 as a linker molecule in breast cancer Specific Aim 2 To determine the role of functional regulation of p85 in breast cancer cells Specific Aim 3 To determine the role of p85 in the initiation and progression of breast cancer development in transgenic mice.